Letter by Giblett and Hoole Regarding Article, ''Remote Ischemic Postconditioning During Percutaneous Coronary Interventions: Remote Ischemic Postconditioning-Percutaneous Coronary Intervention Randomized Trial'' Joel P. Giblett and Stephen P. Hoole Circ Cardiovasc Interv. 2014;7:422 doi: 10.1161/CIRCINTERVENTIONS.114.001527 Circulation: Cardiovascular Interventions is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 1941-7640. Online ISSN: 1941-7632
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circinterventions.ahajournals.org/content/7/3/422
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Correspondence Letter by Giblett and Hoole Regarding Article, “Remote Ischemic Postconditioning During Percutaneous Coronary Interventions: Remote Ischemic Postconditioning-Percutaneous Coronary Intervention Randomized Trial” To the Editor: We read with interest the article written by Lavi et al.1 However, we are concerned that there seem to be several limitations in their methodological design that may have led to the failure of their remote postconditioning trial to show benefit in elective percutaneous coronary intervention. The first is that by the time the threshold for conditioning was met, the window for cardioprotection had likely closed. Ischemic conditioning requires a threshold dose to be reached to trigger maximal conditioning and prevent ischemia–reperfusion injury. Unfortunately, the conditioning protocol in this study only achieved this threshold 25 minutes after percutaneous coronary intervention and a long time after the majority of ischemia–reperfusion injury occurs. Therefore, it is not surprising that cardioprotection was not observed.2 A better mode of delivery would have been to apply ischemic conditioning during diagnostic angiography and certainly before stent deployment. The second limitation, which the authors acknowledge, is the inclusion of unstable patients. These subjects may have had recent intermittent myocardial ischemia, providing local ischemic preconditioning that may have protected the myocardium in the control group.3 This does not rule out potential benefit for remote postconditioning in ST-segment–elevation myocardial infarction in which the ischemic insult is unheralded. Third, a significant proportion of subjects in the trial had diabetes mellitus. Evidence from both animal and human studies has demonstrated an elevated threshold to condition the diabetic heart, requiring ≥4 cycles to achieve cardioprotection.4 Underdosing of this group may have underpowered the study.
Remote ischemic conditioning remains an attractive therapy after percutaneous coronary intervention but only if the laws of conditioning are obeyed.5 It is important that conditioning trials are designed to take full advantage of the characteristic temporal pattern and dose dependency of cardioprotection.
Disclosures None. Joel P. Giblett, BM, BSc, MRCP Stephen P. Hoole, MA, MRCP, DM Department of Interventional Cardiology Papworth Hospital Cambridge, United Kingdom
References 1. Lavi S, D’Alfonso S, Diamantouros P, Camuglia A, Garg P, Teefy P, Jablonsky G, Sridhar K, Lavi R. Remote ischemic postconditioning during percutaneous coronary interventions: remote ischemic postconditioning-percutaneous coronary intervention randomized trial. Circ Cardiovasc Interv. 2014;7:225–232. 2. Vander Heide RS, Steenbergen C. Cardioprotection and myocardial reperfusion: pitfalls to clinical application. Circ Res. 2013;113:464–477. 3. Lorgis L, Gudjoncik A, Richard C, Mock L, Buffet P, Brunel P, JaninManificat L, Beer JC, Brunet D, Touzery C, Rochette L, Cottin Y, Zeller M. Pre-infarction angina and outcomes in non-ST-segment elevation myocardial infarction: data from the RICO survey. PLoS One. 2012;7:e48513. 4. Sivaraman V, Hausenloy DJ, Wynne AM, Yellon DM. Preconditioning the diabetic human myocardium. J Cell Mol Med. 2010;14(6B):1740–1746. 5. Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O’Sullivan M, Dutka DP. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation. 2009;119:820–827.
(Circ Cardiovasc Interv. 2014;7:422.) © 2014 American Heart Association, Inc. Circ Cardiovasc Interv is available at http://circinterventions.ahajournals.org
DOI: 10.1161/CIRCINTERVENTIONS.114.001527
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The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circinterventions.ahajournals.org/content/7/3/422
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation: Cardiovascular Interventions can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation: Cardiovascular Interventions is online at: http://circinterventions.ahajournals.org//subscriptions/
Downloaded from http://circinterventions.ahajournals.org/ by guest on July 9, 2014
Correspondence Letter by Giblett and Hoole Regarding Article, “Remote Ischemic Postconditioning During Percutaneous Coronary Interventions: Remote Ischemic Postconditioning-Percutaneous Coronary Intervention Randomized Trial” To the Editor: We read with interest the article written by Lavi et al.1 However, we are concerned that there seem to be several limitations in their methodological design that may have led to the failure of their remote postconditioning trial to show benefit in elective percutaneous coronary intervention. The first is that by the time the threshold for conditioning was met, the window for cardioprotection had likely closed. Ischemic conditioning requires a threshold dose to be reached to trigger maximal conditioning and prevent ischemia–reperfusion injury. Unfortunately, the conditioning protocol in this study only achieved this threshold 25 minutes after percutaneous coronary intervention and a long time after the majority of ischemia–reperfusion injury occurs. Therefore, it is not surprising that cardioprotection was not observed.2 A better mode of delivery would have been to apply ischemic conditioning during diagnostic angiography and certainly before stent deployment. The second limitation, which the authors acknowledge, is the inclusion of unstable patients. These subjects may have had recent intermittent myocardial ischemia, providing local ischemic preconditioning that may have protected the myocardium in the control group.3 This does not rule out potential benefit for remote postconditioning in ST-segment–elevation myocardial infarction in which the ischemic insult is unheralded. Third, a significant proportion of subjects in the trial had diabetes mellitus. Evidence from both animal and human studies has demonstrated an elevated threshold to condition the diabetic heart, requiring ≥4 cycles to achieve cardioprotection.4 Underdosing of this group may have underpowered the study.
Remote ischemic conditioning remains an attractive therapy after percutaneous coronary intervention but only if the laws of conditioning are obeyed.5 It is important that conditioning trials are designed to take full advantage of the characteristic temporal pattern and dose dependency of cardioprotection.
Disclosures None. Joel P. Giblett, BM, BSc, MRCP Stephen P. Hoole, MA, MRCP, DM Department of Interventional Cardiology Papworth Hospital Cambridge, United Kingdom
References 1. Lavi S, D’Alfonso S, Diamantouros P, Camuglia A, Garg P, Teefy P, Jablonsky G, Sridhar K, Lavi R. Remote ischemic postconditioning during percutaneous coronary interventions: remote ischemic postconditioning-percutaneous coronary intervention randomized trial. Circ Cardiovasc Interv. 2014;7:225–232. 2. Vander Heide RS, Steenbergen C. Cardioprotection and myocardial reperfusion: pitfalls to clinical application. Circ Res. 2013;113:464–477. 3. Lorgis L, Gudjoncik A, Richard C, Mock L, Buffet P, Brunel P, JaninManificat L, Beer JC, Brunet D, Touzery C, Rochette L, Cottin Y, Zeller M. Pre-infarction angina and outcomes in non-ST-segment elevation myocardial infarction: data from the RICO survey. PLoS One. 2012;7:e48513. 4. Sivaraman V, Hausenloy DJ, Wynne AM, Yellon DM. Preconditioning the diabetic human myocardium. J Cell Mol Med. 2010;14(6B):1740–1746. 5. Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O’Sullivan M, Dutka DP. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study: a prospective, randomized control trial. Circulation. 2009;119:820–827.
(Circ Cardiovasc Interv. 2014;7:422.) © 2014 American Heart Association, Inc. Circ Cardiovasc Interv is available at http://circinterventions.ahajournals.org
DOI: 10.1161/CIRCINTERVENTIONS.114.001527
Downloaded from http://circinterventions.ahajournals.org/ by guest on July 9, 2014 422
